SBIR Phase I: Highly Active and Selective Hydroxylation Catalysts for Combinatorial Biocatalysis

Altus Biologics Inc, Cambridge MA

Investigators

Abstract

This Small Business Innovation Research (SBIR) Phase I project will demonstrate the feasibility of using "directed evolution" to create highly active, selective hydroxylation enzymes for use in combinatorial biocatalysis of potential drugs. Such protein catalysts will be capable of direct hydroxylation of non-activated carbon centers without oxidation of other sensitive functionality; a transformation that is virtually impossible using traditional chemistry. Using highly active bacterial enzymes as a starting point, random mutants will be generated and clones capable of targeted hydroxylations will be selected by using by using high-through-put screening methods. Existing bacterial P450 enzymes do not have the required selectivity. Mammalian P450 systems that work effectively in-vivo, are difficult to express and are slow in catalysis. The potential of this technology for combinatorial library creation will be demonstrated using drug scaffolds. The commercial application of the proposed technology will initially be to provide research oxidation catalysts for the development of new drug candidates. New classes of oxygenated candidates for testing will be prepared. Subsequently, the catalysts may be used in the actual synthesis of the new drugs.